A major obstacle in the treatment of spinal cord injury (SCI) is the incapacity of damaged axons to regenerate in the mammalian central nervous system (CNS). The regenerative failure of CNS neurons is primarily a consequence of the growth hostile environment rather than an intrinsic inability of adult neurons to regrow injured axons (Savio and Schwab, 1990; Li and Raisman, 1994). Adult CNS myelin is a major source for a variety of growth inhibitory molecules (Fournier and Strittmatter, 2001). Myelin is produced by oligodendrocytes, a glial cell type that forms extended membrane structures that are in close contact with many long projecting axons. Three potent myelin-derived growth-inhibitory proteins have been identified: myelin associated-glycoprotein (MAG), Nogo, and oligodendrocyte-myelin glycoprotein (OMgp) (McKerracher et al., 1994; Mukhopashyay et al., 1994; Chen et al., 2000; GrandPre et al. 2000; Prinjha et al, 2000; Kottis et al., 2002; Wang et al., 2002a). These molecules are all localized to the periaxonal membrane, participate in axon-glia interactions, and are thought to limit neuronal sprouting and structural plasticity in the adult mammalian CNS.